ABSTRACT
MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that negatively regulate the expression of their target genes. They are involved in many biological processes, including cell proliferation, apoptosis and differentiation, and are considered as promising new therapeutic targets for cancer. However, the identity of miRNAs involved in apoptosis and their respective targets remain largely unknown. Given the elevated complexity of miRNA regulation of gene expression, we performed a functional screening as an alternative strategy to identify those miRNAs that in lung cancer cells may interfere with the apoptotic process. To this aim, we generated a derivative of the non-small cell lung carcinoma A549 cell line in which caspase-8, a critical upstream initiator of apoptosis, can be activated by administration of the small dimerizer drug AP20187. We found a number of miRNAs that may rescue cell viability from caspase-8 activation. They included miRNAs already described as oncogenic such as miR-17, miR-135 and miR-520, but also some miRNAs such as miR-124-1 and miR-34c for which a tumor-suppressive role has instead been described or expected. Among them, miR-34c-5p markedly increased resistance to paclitaxel-induced apoptosis. We demonstrate that Bmf (Bcl-2-modifying factor) is a target of miR-34c-5p, and that its silencing, together with that of c-myc, a known target of miR-34c-5p, contributes to resistance to apoptosis induced by paclitaxel through p53 downregulation.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , MicroRNAs/genetics , Paclitaxel/pharmacology , Base Sequence , Caspase 8/metabolism , Cell Line, Tumor , Humans , MicroRNAs/metabolismABSTRACT
Gliomas are the most common primary central nervous system tumors with a dismal prognosis. Despite recent advances in surgery, radiotherapy, and chemotherapy, current treatment regimens have a modest survival benefit. A crucial challenge is to deliver drugs effectively to invasive glioma cells residing in a sanctuary within the central nervous system. New therapies are essential, and oligonucleotide-based approaches, including antisense, microRNAs, small interfering RNAs, and nucleic acid aptamers, may provide a viable strategy. Thanks to their unique characteristics (low size, good affinity for the target, no immunogenicity, chemical structures that can be easily modified to improve their in vivo applications), these molecules may represent a valid alternative to antibodies particularly to overcome challenges presented by the blood-brain barrier. Here we will discuss recent results on the use of oligonucleotides that will hopefully provide new effective treatment for gliomas.
ABSTRACT
La Anemia Ferropénica es el descenso de hemoglobina en sangre secundaria a una disminución de la concentración de hierro en el organismo. Su aporte insuficiente en la dieta es la principal causa y produce en los niños alteraciones en la conducta, pérdida de apetito, pica. Se planteó como objetivo general determinar la prevalencia de anemia ferropénica de niños internos de la Escuela Hogar Juan D. Perón y relacionarla con la edad, sexo y estdo nutricional del niño. De 345 niños internos se tomaron al azar 130 clínicamente sanos según el informe clínico, se los agrupó en intervalos por edades y se realizó un examen clínico y de laboratorio. La mayor prevalencia de Anemia Ferrpénica se halló en los varones entre 8 y 11 años de edad, todos ellos eutróficos, resultado que no concuerdan con otros autores. Se concluye que el mayor porcentaje en varones podría deberse a que estan en crecimiento y los requerimientos nutricionales son mayores, como así también a un aporte insuficiente en este micronutriente. Se sugieren medidas preventivas (AU)
Subject(s)
Child, Preschool , Male , Humans , Female , Child , Adolescent , Group Homes , Anemia, Iron-Deficiency/epidemiology , Anemia, Iron-Deficiency/epidemiology , Argentina , Anemia, Iron-Deficiency/complications , Nutritional Status , Child Nutrition Disorders/complications , Epidemiologic Studies , Anemia, Iron-Deficiency/complicationsABSTRACT
La Anemia Ferropénica es el descenso de hemoglobina en sangre secundaria a una disminución de la concentración de hierro en el organismo. Su aporte insuficiente en la dieta es la principal causa y produce en los niños alteraciones en la conducta, pérdida de apetito, pica. Se planteó como objetivo general determinar la prevalencia de anemia ferropénica de niños internos de la Escuela Hogar Juan D. Perón y relacionarla con la edad, sexo y estdo nutricional del niño. De 345 niños internos se tomaron al azar 130 clínicamente sanos según el informe clínico, se los agrupó en intervalos por edades y se realizó un examen clínico y de laboratorio. La mayor prevalencia de Anemia Ferrpénica se halló en los varones entre 8 y 11 años de edad, todos ellos eutróficos, resultado que no concuerdan con otros autores. Se concluye que el mayor porcentaje en varones podría deberse a que estan en crecimiento y los requerimientos nutricionales son mayores, como así también a un aporte insuficiente en este micronutriente. Se sugieren medidas preventivas
Subject(s)
Child, Preschool , Male , Humans , Female , Child , Adolescent , Anemia, Iron-Deficiency/epidemiology , Anemia, Iron-Deficiency , Group Homes , Anemia, Iron-Deficiency/complications , Anemia, Iron-Deficiency , Argentina , Epidemiologic Studies , Nutritional Status , Child Nutrition Disorders/complicationsABSTRACT
Diffusion-weighted magnetic resonance imaging (DW-MRI) of the brain was performed in two patients with methylmalonic aciduria who presented signs and symptoms of neurological involvement without metabolic decompensation. Patient 1 presented acute metabolic stroke and patient 2 presented subacute encephalopathy. Brain DW-MRI confirmed very recent damage in patient 1, while the absence of brain lesions on brain DW-MRI indicates the development of more chronic damage in patient 2. Brain DW-MRI represents an additional and complementary tool in the assessment of brain damage in methylmalonic aciduria patients who develop neurological syndrome.
